Phase 2 Multicenter Open-Label Study on Efficacy, Safety, and Tolerability of Riliprubart in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Trial ID: 2024-512345-16-00
Protocol: PDY16744
Sponsor: Sanofi-Aventis Recherche & Developpement

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Diseases & Conditions

Chronic inflammatory demyelinating polyradiculoneuropathy

Objectives

The primary objective of this study is to evaluate the **efficacy** of SAR445088 in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) across three subpopulations: standard of care (SOC)-Treated, SOC-Refractory, and SOC-Naive. Additionally, the study aims to assess the long-term safety and tolerability of SAR445088 in CIDP. This is clinically relevant as it addresses the need for effective treatment options for different patient subgroups within CIDP, a condition characterized by progressive weakness and impaired sensory function in the legs and arms.

Secondary objectives include:

Part A: Assessing the safety and tolerability of SAR445088 in CIDP.
Part A: Evaluating the immunogenicity of SAR445088.
Part A: Determining the efficacy of SAR445088 with overlapping SOC in the SOC-Treated group.
Part B: Investigating the durability of efficacy during long-term treatment with SAR445088 in CIDP.
Part B: Evaluating the long-term immunogenicity of SAR445088 in CIDP.

These secondary objectives are crucial for understanding the comprehensive impact of SAR445088 on CIDP, including its safety profile, immune response, and sustained effectiveness over time.

Participants

The clinical trial involves a total of **42 participants** diagnosed with **Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)**. The study population includes both male and female adults aged 18 years and older. Participants were selected based on a documented definite or probable diagnosis of CIDP, with subgroups categorized as standard-of-care (SOC)-Treated, SOC-Refractory, or SOC-Naïve. The trial includes individuals who are capable of providing informed consent and have documented vaccinations against encapsulated bacterial pathogens within the last five years or initiated at least 14 days prior to the first dose. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to specific contraceptive measures if applicable. The trial does not exclude vulnerable populations, and both genders are represented. The selection criteria ensure that participants have a stable health status concerning their CIDP treatment history and current condition.

Plans and Procedures

The clinical trial is a Phase 2, multicenter, open-label, non-randomized, proof-of-concept study designed to evaluate the efficacy, safety, and tolerability of **riliprubart** in adults with **chronic inflammatory demyelinating polyradiculoneuropathy** (CIDP). The trial is structured into two parts: Part A focuses on the efficacy of SAR445088 across three subpopulations of CIDP patients—standard of care (SOC)-Treated, SOC-Refractory, and SOC-Naive—while Part B assesses the long-term safety and tolerability of the treatment. The study is expected to conclude by September 2026, with participant recruitment having commenced in October 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, documented diagnosis of CIDP, and vaccination status. The trial includes follow-up visits to monitor the treatment's effects and any adverse events. The end-of-study visit will evaluate the overall outcomes and collect final data. The expected length of participant involvement is up to 100 weeks, with conditions for early termination including significant adverse events or withdrawal of consent.

Key elements of the research methodology include the administration of riliprubart via subcutaneous injection, with a maximum daily dose of 600 mg. The primary endpoints for Part A include the percentage of participants relapsing after SOC withdrawal and during the SAR445088 treatment period, and the percentage of participants responding during the treatment period for SOC-Refractory and SOC-Naive groups. Part B's primary endpoint is the number of participants reported with adverse events. Secondary endpoints include the incidence of anti-SAR445088 antibodies and the percentage of participants with sustained response during the treatment extension period.

Treatment

The clinical trial involves the administration of **riliprubart**, an experimental medication developed by Sanofi Aventis Recherche et Développement (SAR). Riliprubart is formulated as a **solution for injection** and is intended for **subcutaneous use**. The active substance, riliprubart, is classified as a protein of other origin. The maximum daily dose of riliprubart is 600 mg, with a total maximum dose of 600 mg over the course of the treatment period, which spans up to 100 days. The medication is administered to evaluate its efficacy, safety, and tolerability in adults diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP).

In addition to the experimental treatment, the study includes standard-of-care (SOC) therapy as a non-experimental treatment. Participants are categorized into three subpopulations: SOC-treated, SOC-refractory, and SOC-naive. The trial aims to assess the efficacy of riliprubart across these subpopulations, as well as to evaluate the long-term safety and tolerability of the medication. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy

The efficacy of SAR445088 in the treatment of **chronic inflammatory demyelinating polyneuropathy (CIDP)** will be assessed through a series of primary and secondary endpoints. In Part A of the study, the primary endpoints include the percentage of participants relapsing after withdrawal of standard of care (SOC) and during the SAR445088 treatment period for SOC-Treated patients, and the percentage of participants responding during the SAR445088 treatment period for SOC-Refractory and SOC-Naïve patients. In Part B, the primary endpoint is the number of participants reported with adverse events.

Secondary endpoints in Part A include the number of participants reported with adverse events, the incidence and titer of anti-SAR445088 antibodies (ADA), and the percentage of participants in the SOC-Treated group improving during the overlap treatment period. In Part B, secondary endpoints include the percentage of SOC-Treated participants who remain relapse-free during the treatment extension period, the percentage of SOC-Refractory and SOC-Naïve participants with a sustained response during the treatment extension period, and long-term immunogenicity.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Adults ≥18 years of age at the time of signing the informed consent.
Documented definite or probable diagnosis of CIDP (typical CIDP, pure motor CIDP, or Lewis-Sumner Syndrome) according to the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) Task Force first revision.
Belonging to one of the following three groups: standard-of-care (SOC)-Treated, SOC-Refractory or SOC-Naïve, as defined below. - SOC-Treated (all criteria a-c must be met): a) Documented evidence of objective response to SOC, with clinically meaningful improvement. Clinically meaningful improvement is defined as one of the following: ≥1-point decrease in adjusted INCAT score, ≥4 points increase in RODS total score, ≥3 points increase in MRC Sum score, ≥8 kilopascal improvement in mean grip strength (one hand), or an equivalent improvement based on information documented in medical records and per the PI’s judgement. b) Must be on stable SOC therapy, defined as no change greater than 10% in frequency or dose of immunoglobulin therapy or corticosteroids within 8 weeks prior to screening, remaining at stable SOC therapy until the time of first SAR445088 dosing. c) Evidence of clinically meaningful deterioration on interruption or dose reduction of SOC therapy within 24 months prior to screening, determined by clinical examination or medical records. Clinically meaningful deterioration is defined as one of the following: ≥1-point increase in adjusted INCAT score, decrease in RODS total score ≥4 points, decrease in MRC Sum score ≥3, mean grip strength worsening of ≥8 kilopascals (one hand), or an equivalent deterioration based on information from medical records and at the PI’s judgement. - SOC-Refractory (all criteria a-d must be met): a) Evidence of failure or inadequate response to SOC defined as no clinically meaningful improvement and persistent INCAT score ≥2 after treatment for a minimum of 12 weeks on SOC prior to screening. A clinically meaningful improvement is defined as one of the following: ≥1-point decrease in adjusted INCAT score, increase in RODS total score ≥4 points, increase in MRC Sum score ≥3, mean grip strength improvement of ≥8 kilopascals (one hand), or equivalent improvement based on information from medical records and at the PI’s judgement. Or - Unable to receive or continue treatment with immunoglobulins or corticosteroids due to side effects. - b) Patient has not received immunoglobulins (IVIg or SCIg) within 12 weeks prior to screening. c) Certain immunosuppressant drugs are allowed in this group if taken for ≥6 months and at a stable dose for ≥3 months prior to screening: azathioprine, methotrexate, mycophenolate mofetil and cyclosporine. Oral corticosteroids are allowed if on a stable dose of <20 mg/day of prednisone (or equivalent dose for other oral corticosteroids) for ≥3 months prior to screening. d) INCAT score: 2-9 (a score of 2 should be exclusively from leg disability component of INCAT). - SOC-Naïve (all criteria a-c must be met): a) Participants without previous treatment for CIDP or participants who received immunoglobulins (IVIg or SCIg) or corticosteroids but were stopped for reasons other than lack of response or side effects. b) Not treated with immunoglobulins (IVIg or SCIg) or corticosteroids for at least 6 months prior to screening. c) INCAT score: 2-9 (a score of 2 should be exclusively from leg disability component of INCAT.
Documented vaccinations against encapsulated bacterial pathogens given within 5 years of enrollment or initiated a minimum of 14 days prior to first dose
A female participant must use a double contraception method including a highly effective method of birth control from inclusion and up to 52 weeks plus 30 days after the last study dose and agree not to donate eggs, ova or oocytes during this period.
A female participant must have a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours before the first dose of study intervention.
Male participants, whose partners are of childbearing potential must accept to use, during sexual intercourse, a double contraceptive method according to the following: condom plus an additional highly effective contraception
Male participants must have agreed not to donate sperm during the intervention and up to 52 weeks after the last dose.
Capable of giving signed informed consent

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Exclusion Criteria

Polyneuropathy of other causes, including but not limited to hereditary demyelinating neuropathies, neuropathies secondary to infection or systemic disease, diabetic neuropathy, drug- or toxin-induced neuropathies, multifocal motor neuropathy, polyneuropathy related to IgM monoclonal gammopathy, POEMS syndrome, lumbosacral radiculoplexus neuropathy, pure sensory CIDP and acquired demyelinating symmetric (DADS) neuropathy (also known as distal CIDP).
Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments.
Poorly controlled diabetes (HbA1c >7%).
Serious infections requiring hospitalization within 30 days prior to screening and any active infection requiring treatment during screening.
Clinical diagnosis of SLE.
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Specifically, history of any hypersensitivity reaction to SAR445088 or its components or of a severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibody.
Participants with a history of suicidality in the six months prior to screening or currently at risk of committing suicide.
Presence of conditions (medical history or laboratory assessments) that may predispose the participant to excessive bleeding or increased risk of infection.
Evidence of CIDP relapse within 6 weeks after receiving a vaccination.
Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk.
Treatment with plasma exchange within 12 weeks prior to screening.
Prior treatment with rituximab or ocrelizumab in the 6 months prior to SAR445088 dosing or until return of B-cell counts to normal levels, whichever is longer.
Immunosuppressive/chemotherapeutic medications such as azathioprine, methotrexate, cyclophosphamide, cyclosporine, mycophenolate mofetil, tacrolimus, interferon, TNF-alpha inhibitor: within 6 months prior to dosing (except for some cases as indicated in the SOC-Refractory group).
Treatment (any time) with highly immunosuppressive/chemotherapeutic medications with sustained effects, eg, mitoxantrone, alemtuzumab, cladribine.
Treatment (any time) with total lymphoid irradiation or bone marrow transplantation.
Use of any specific complement system inhibitor (eg, eculizumab) within 12 weeks or 5 times the half-life of the product, whichever is longer, prior to screening.
Pregnant (defined as positive β-HCG blood test) or lactating females.
Positive result on any of the following tests: hepatitis B surface (HBsAg) antigen, anti-hepatitis B core antibodies (anti-HBc Ab)-unless anti-hepatitis B surface antibodies (anti-HBs Ab) are also positive , indicating natural immunity-, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 antibodies).
Evidence of IgG4 autoantibodies against paranodal proteins (NF155 and CNTN1).

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Not Recruiting	13 Oct 2021	16
Germany	Not Recruiting	13 Oct 2021	7
Italy	Not Recruiting	13 Oct 2021	10
The Netherlands	Not Recruiting	13 Oct 2021	—
Poland	Not Recruiting	13 Oct 2021	9
Spain	Not Recruiting	13 Oct 2021	11
Netherlands	—	—	3